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Monocyte chemoattractant protein-1 (MCP-1) exerts a crucial effect on obesity-related monocytes\/macrophages infiltration. Clinically, aspirin and salsalate are beneficial for the treatment of metabolic diseases in which adipose tissue inflammation plays an essential role. Herein, we investigated the effect and precise mechanism of their active metabolite salicylate on TNF-\u03b1-elevated MCP-1 in adipocytes. The results indicated that salicylate sodium (SAS) could lower the level of MCP-1 in TNF-\u03b1-stimulated adipocytes, which resulted from a previously unrecognized target phosphodiesterase (PDE), 3B (PDE3B), rather than its known targets IKK\u03b2 and AMPK. The SAS directly bound to the PDE3B to inactivate it, thus elevating the intracellular cAMP level and activating PKA. Subsequently, the expression of MKP-1 was increased, which led to the decrease in p-EKR and p-p38. Both PDE3B silencing and the pharmacological inhibition of cAMP\/PKA compromised the suppressive effect of SAS on MCP-1. In addition to PDE3B, the PDE3A and PDE4B activity was also inhibited by SAS. Our findings identify a previously unrecognized pathway through which SAS is capable of attenuating the inflammation of adipocytes.<\/jats:p>","DOI":"10.3390\/ijms24010320","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T04:40:39Z","timestamp":1672116039000},"page":"320","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Salicylate Sodium Suppresses Monocyte Chemoattractant Protein-1 Production by Directly Inhibiting Phosphodiesterase 3B in TNF-\u03b1-Stimulated Adipocytes"],"prefix":"10.3390","volume":"24","author":[{"given":"Xiaoyu","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Gao","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuangzhuang","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Kang","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ximeng","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenlu","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Peng","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7860-6932","authenticated-orcid":false,"given":"Yun","family":"Qi","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1172\/JCI200319246","article-title":"Obesity is associated with macrophage accumulation in adipose tissue","volume":"112","author":"Weisberg","year":"2003","journal-title":"J. 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